Late-onset Pompe disease (LOPD) is a progressive metabolic myopathy characterized by spinal muscle weakness, pulmonary decline, and early death. Morbidity and mortality result primarily from progressive respiratory muscle weakness involving the inspiratory and expiratory muscles. Drug therapy (enzyme replacement therapy) is available but effects on pulmonary function and respiratory strength are modest. Therefore, treatments that target respiratory weakness in LOPD are an unmet clinical need. To counteract respiratory weakness in LOPD, we have developed a respiratory muscle training (RMT) program. Hand-held RMT devices provide individualized, calibrated pressure-threshold resistance against inspiration and expiration. Counteracting weakness with exercise training offers a biologically plausible mechanism of action. Our preliminary research in 8 adults with LOPD reveals our 12-week RMT program results in large to very large increases in inspiratory and expiratory strength. Exploratory outcomes suggest these strength increases may also have positive effects on motor function. We propose an exploratory, double-blind, placebo- controlled, randomized clinical trial (RCT) of our 12-week RMT program in LOPD to determine if a future efficacy trial is warranted. Our Patient Advocacy Committee has confirmed the meaningfulness of the research and outcomes, and provided input on recruitment and subject burden. In a minimal risk study, 24 adults with LOPD will be randomized to treatment (RMT) or control (sham-RMT) arms. All subjects and researchers will be blinded to study arm except the clinician providing RMT therapy. Assessments will be conducted at pretest, posttest, and after 3- and 6-months detraining. Our primary outcome measure is maximum inspiratory pressure (MIP), an index of inspiratory strength. Secondary outcomes include maximum expiratory pressure (MEP), 6-Minute Walk Test (6MWT), Gait, Stairs, Gower, and Chair (GSGC) scale, peak cough flow (PCF), and patient-reported life activity/social participation. Exploratory outcomes target sleep and sleep breathing, including quantitative measures from polysomnography (PSG) and patient-reported measures of fatigue, daytime sleepiness, and sleep quality. Our Specific Aims will determine: 1) the utility and feasibility of sham- RMT as a control condition for RMT and 2) the outcomes that are clinically meaningful to patients and clinicians. The aims will determine if a future efficacy trial is warranted and if so inform its design, conduct, and analysis. Critically, his research will provide definitive evidence as to whether sham-RMT is a useful, feasible control and test an expanded set of outcomes in a larger group of subjects to allow the selection of functional measures for future efficacy testing.